This application is in response to a Request for Application (RFA-HD-10-018) to conduct community-linked studies to investigate the role of prenatal alcohol exposure in the risk for SIDS, stillbirth and FASD, and to determine how these different outcomes are inter-related, The proposed research will be conducted by the investigators the Prenatal Alcohol, SIDS and Stillbirth (PASS) Research Network in a cooperative agreement with NICHD and NIAAA. This research involves the collaboration of: 1) two comprehensive clinical sites serving populations that are high risk for prenatal alcohol exposure, SIDS, and stillbirth, i.e. the American Indians in the Northern Plains and the Cape Coloured in Cape Town, South Africa;2) a central Developmental Biology and Pathology Centre (DBPC);3) a central Data Coordinating and Analysis Center (DCAC);4) a central Physiology Assessment Center (PAC);and 5) program scientists and officers at the NICHD and NIAAA. The mission of our site is to accomplish the 9 Specific Aims of the Safe Passage Study through the recruitment and enrollment of 7,000 women and the performance of all of the hypothesis-driven study protocols involving the maternal/fetal dyads. The SCCS is overseeing the performance and analysis of Specific Aim 3. This aim is to determine the role of prenatal alcohol exposure, as potentially modified by other environmental, genetic, and placental factors, upon the facial features, somatic growth, and neurological/brain development in the fetus and infant utilizing fetal ultrasonography and infant facial imaging and standardized feature assessment. We will test the hypotheses that: 1) prenatal alcohol exposure adversely impacts facial, somatic, and/or brain growth in the human fetus as early as 20-24 gestational weeks, i.e., the earliest time-point examined by us;2) prenatal alcohol exposure is associated with facial dysmorphology that is identified by imaging of the face as early as 20-24 weeks and remains present at 1 postnatal month and 12 postnatal months;and 3) this alcohol toxicity is modified by other environmental and placental factors, such as maternal nutrition, maternal smoking, and placental perfusion failure. PUBLIC HEALTH RELEVANCE: Heavy drinking during pregnancy in many disadvantaged communities in South Africa is of great concern. This study will identify additional adverse effects of alcohol on the placenta and developing fetus. More information on the adverse effects will strengthen campaigns against drinking during pregnancy.